Cornforth reagent → 1-tert-Butyl 2-methyl (2R)-4-oxopyrrolidine-1,2-dicarboxylate

To slurry of pyridinium dichromate (9.97 g, 26.5 mmol) in dichloromethane (60 mL) at rt was added (2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (5.00 g, 20.39 mmol) in several portions. The resulting mixture was stirred overnight at rt. Celite (5 g) was added and the mixture stirred for 40 min, filtered and the filter cake was rinsed with additional dichloromethane (50 mL×3). The resulting filtrate was concentrated and toluene (40 mL) was added followed by concentration again under vacuum to give ˜6.5 g of a brown syrup as the crude product. Purification by flash silica gel chromatography (120 g column, EtOAc in Hexane, 0 to 100% gradiant, 85 mL/min) afforded 4.18 g (84%) of the title compound as a white solid. LCMS (condition A): m/z 144 (M-Boc) −ve. 1H NMR (400 MHz, CDCl3) δ ppm 4.64-4.89 (1 H, m), 3.84-3.96 (2 H, m), 3.77 (3 H, s), 2.81-3.10 (1 H, m), 2.59 (1 H, dd, J=18.93, 1.76 Hz), 1.52 (9 H, s).

1. additionCelite (5 g) was added
2. stirringthe mixture stirred for 40 min
3. filtrationfiltered
4. washthe filter cake was rinsed with additional dichloromethane (50 mL×3)
5. concentrationThe resulting filtrate was concentrated
6. additiontoluene (40 mL) was added
7. concentrationfollowed by concentration again under vacuum

ORD record

ord-990fe9ec1d174545930ea8e5f37ee126

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921368B2